Reaction Acceleration Promoted by Partial Solvation at the Gas/Solution Interface
TL;DR: The kinetics of organic reactions of different types in microvolumes (droplets, thin films, and sealed tubes) show effects of gas/solution interfacial area, reaction molecularity and solvent polarity as discussed by the authors.
Abstract: The kinetics of organic reactions of different types in microvolumes (droplets, thin films, and sealed tubes) show effects of gas/solution interfacial area, reaction molecularity and solvent polarity. Partial solvation at the gas/solution interface is a major contributor to the 104 -fold reaction acceleration seen in bimolecular but not unimolecular reactions in microdroplets. Reaction acceleration can be used to manipulate selectivity by solvent choice.
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TL;DR: In this paper , it was revealed that pure water has an additional shimmering buzz arising from electron transfer between neighboring water molecules, in which the hydrogen atom on one water molecule forms a hydrogen bond with a neighbor's oxygen atom.
Abstract: Description Hydrogen bond charge transfer in water may have far-reaching chemical implications Water is far more than a collection of neutral H2O molecules, linked by hydrogen bonds, with a trace of hydrogen (H+) and hydroxide (OH−) ions. Indeed, recent work has revealed that pure water has an additional shimmering buzz arising from electron transfer between neighboring water molecules, in which the hydrogen atom on one water molecule forms a hydrogen bond with a neighbor’s oxygen atom (1–4). This charge transfer, and the resulting attraction between the pair of oppositely charged water molecules, contributes to the strength of the hydrogen bonds among water molecules (4). Hydrogen-bonding defects in liquid water lead to the accumulation of negative or positive charge on water molecules with an odd number of hydrogen bonds (2–4). These charged waters may play an overlooked role in chemical reactions at the air–water and oil–water interfaces that are ubiquitous in biological, geological, and environmental chemistry.
20 citations
22 Aug 2022
TL;DR: In this article , the authors reported the concurrent conversion of several phosphonates to phosphonic acids by reduction (R−P → H−P) and to pentavalent phosphoric acids by oxidation.
Abstract: Abstract Microdroplets show unique chemistry, especially in their intrinsic redox properties, and to this we here add a case of simultaneous and spontaneous oxidation and reduction. We report the concurrent conversions of several phosphonates to phosphonic acids by reduction (R−P → H−P) and to pentavalent phosphoric acids by oxidation. The experimental results suggest that the active reagent is the water radical cation/anion pair. The water radical cation is observed directly as the ionized water dimer while the water radical anion is only seen indirectly though the spontaneous reduction of carbon dioxide to formate. The coexistence of oxidative and reductive species in turn supports the proposal of a double‐layer structure at the microdroplet surface, where the water radical cation and radical anion are separated and accumulated.
19 citations
TL;DR: In this paper , the formation of a molecular adduct with the water radical cation is observed in the positive ion mass spectrum while its formation in the interfacial region of the microdroplet (i.e., at the air-droplet interface) is indicated by the strong dependence of the oxidation product formation on the spray distance and the solvent composition.
Abstract: Spontaneous oxidation of compounds containing diverse X=Y moieties (e.g., sulfonamides, ketones, esters, sulfones) occurs readily in organic-solvent microdroplets. This surprising phenomenon is proposed to be driven by the generation of an intermediate species [M+H2O]+·: a covalent adduct of water radical cation (H2O +· ) with the reactant molecule (M). The adduct is observed in the positive ion mass spectrum while its formation in the interfacial region of the microdroplet (i.e., at the air-droplet interface) is indicated by the strong dependence of the oxidation product formation on the spray distance (which reflects the droplet size and consequently the surface-to-volume ratio) and the solvent composition. Importantly, based on the screening of a ca. 21,000-compound library and the detailed consideration of six functional groups, the formation of a molecular adduct with the water radical cation is a significant route to ionization in positive ion mode electrospray, where it is favored in those compounds with X=Y moieties which lack basic groups. A set of model monofunctional systems was studied and in one case, benzyl benzoate, evidence was found for oxidation driven by hydroxyl radical adduct formation followed by protonation in addition to the dominant water radical cation addition process. Significant implications of molecular ionization by water radical cations for oxidation processes in atmospheric aerosols, analytical mass spectrometry and small-scale synthesis are noted.
19 citations
TL;DR: In this paper , the potential value of high-throughput desorption electrospray ionization mass spectrometry (HT DESI-MS) for small-scale rapid late-stage functionalization (LSF) is investigated.
Abstract: Late-stage functionalization (LSF) of drug molecules is an approach to generate modified molecules that retain functional groups present in the active drugs. Here, we report a study that seeks to characterize the potential value of high-throughput desorption electrospray ionization mass spectrometry (HT DESI-MS) for small-scale rapid LSF. In conventional route screening, HT-based DESI-MS provides contactless, rapid analysis, reliable and reproducible data, minimal sample requirement, and exceptional tolerance to high salt concentrations. Ezetimibe (E), an established hypertension drug, is targeted for modification by LSF. C-H alkenylation and azo-click reactions are utilized to explore this approach to synthesis and analytical characterization. The effect of choice of reactant, stoichiometry, catalyst, and solvent are studied for both reactions using high throughput DESI-MS experiments. Optimum conditions for the formation of LSF products are established with identification by tandem mass spectrometry (MS/MS).
14 citations
TL;DR: It is proposed that the interface of aqueous microdroplets serves as a drying surface that shifts the equilibrium between free amino acids in favor of dehydration via stabilization of the dipeptide isomers, offering a possible solution to the water paradox of biopolymer synthesis in prebiotic chemistry.
Abstract: Significance Enzymes are needed for protein synthesis in vivo because dehydration in water to give amide bonds is highly unfavorable. However, conditions that permit the abiotic production of peptides in aqueous environments are a prerequisite for accepted origin of life chemistry. Here, we report a unique reactivity of free amino acids at the air–water interface of micron-sized water droplets that leads to the formation of peptide isomers on the millisecond timescale. Akin to many plausible prebiotic chemical systems (e.g., sea spray), this reaction is performed under ambient conditions and does not require additional reagents, acid, catalysts, or radiation. These findings exemplify the uniqueness of interfacial physicochemical processes and add support to the potential role of confined-volume systems in abiogenesis.
13 citations
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484 citations
TL;DR: This Minireview introduces droplet and thin-film acceleration phenomena and summarizes recent methods applied to study accelerated reactions in confined-volume, high-surface-area solutions.
Abstract: The striking finding that reaction acceleration occurs in confined-volume solutions sets up an apparent conundrum: Microdroplets formed by spray ionization can be used to monitor the course of bulk-phase reactions and also to accelerate reactions between the reagents in such a reaction. This Minireview introduces droplet and thin-film acceleration phenomena and summarizes recent methods applied to study accelerated reactions in confined-volume, high-surface-area solutions. Conditions that dictate either simple monitoring or acceleration are reconciled in the occurrence of discontinuous and complete desolvation as the endpoint of droplet evolution. The contrasting features of microdroplet and bulk-solution reactions are described together with possible mechanisms that drive reaction acceleration in microdroplets. Current applications of droplet microreactors are noted as is reaction acceleration in confined volumes and possible future scale-up.
274 citations
TL;DR: In this article, it is shown that the environment in the microdroplet differs from that of the bulk: (i) the pH of the solution moves towards the extremes, (ii) the concentrations of the reagents increase, (iii) the relative surface area increases and collision frequencies increase.
Abstract: Functional group derivatization reactions occur in the course of microdroplet/surface collisions in the ambient ionization process of desorption electrospray ionization (DESI). The unique environment in the microdroplet causes rate enhancements of as much as several orders of magnitude in typical bimolecular reactions that proceed through either cationic or anionic intermediates. The environment in the evaporating charged microdroplet differs from that of the bulk: (i) the pH of the solution moves towards the extremes, (ii) the concentrations of the reagents increase, (iii) the relative surface area increases and (iv) collision frequencies increase. The rates of acid-catalyzed reactions, such as the reaction of Girard T reagent with ketosteroids, increase with decreasing pH in positively-charged microdroplets compared to the bulk solution rates. Similarly, the increased pH in evaporating negatively-charged microdroplets contributes to an increase in the rates of base-catalyzed Michael reactions over those recorded under bulk solution conditions. The amount of product formed depends on the reaction time and the droplet size. Nanoelectrospray ionization generates larger droplets than the secondary droplets of DESI so it does not show significant product formation in the analysis period and can be used to analyze products of the DESI experiments. When secondary microdroplets (ca. 1 micron diameter) are generated either by spraying a homogeneous solution of both reagents against an inert surface (reactive DESI) or when a solution of Girard T reagent is sprayed against a solid surface bearing the ketosteroid significant amounts of product are generated. In the case of the Michael reaction with cinnamic acid an alternative dehydrogenated reaction product is formed under microdroplet conditions. Some parallels between the phenomenon reported here and the rate acceleration seen in sonochemistry are noted. The potential value of mass spectrometry in establishing conditions that enhance reaction rates is also indicated. It is possible that these observations will assist in the selection of reaction conditions involving the use of charged microdroplets to enhance the rates of ordinary bulk chemical reactions, especially those involving strong steric hindrance.
252 citations
TL;DR: Reaction thermodynamics is modified by compartmentalization at the mesoscale--without confinement on the molecular scale--leading to a universal mechanism for improving unfavorable reactions.
Abstract: A bimolecular synthetic reaction (imine synthesis) was performed compartmentalized in micrometer-diameter emulsion droplets. The apparent equilibrium constant (Keq) and apparent forward rate constant (k1) were both inversely proportional to the droplet radius. The results are explained by a noncatalytic reaction-adsorption model in which reactants adsorb to the droplet interface with relatively low binding energies of a few kBT, react and diffuse back to the bulk. Reaction thermodynamics is therefore modified by compartmentalization at the mesoscale--without confinement on the molecular scale--leading to a universal mechanism for improving unfavorable reactions.
202 citations